Triosephosphate Isomerase Deficiency, a Unique Glycolytic Enzymopathy

Triosephosphate Isomerase Deficiency, a Unique Glycolytic Enzymopathy 

The classic function of TPI is to adjust the rapid equilibrium between the two triosephosphates, glycerinealdehyde-3-phosphate and DH AP. Patients with TPI deficiency have unimpressive alterations in glucose utilization, ATP and lactate production. Modeling studies and experimental data suggested that the physiological ATP level was maintained due to the activation of enzymes involved in the pen-tosephosphate and glycolytic pathways (Fig. 8.2) [80, 81]. The interconnection of the two pathways with increased activities can compensate for the reduced TPI activity of deficient cells in TPI-deficient erythrocytes [80, 81]. 

Dramatic change in erythrocytes is characterized by the marked increase in DHAP and in a much lesser increase in fructose-1,6-bisphosphate levels [78, 81]. An inverse relationship between TPI activity and DHAP concentration was detected in all TPI-deficient patients. Computer models were evaluated to simulate this inverse relationship in normal and deficient red blood cells [82-84]. However, the low TPI activity-derived DHAP accumulation was not supported by the previous models unless a very low TPI activity was introduced which was not supported by experimental data [82, 84]. Recently, a realistic model of human erythrocyte glycolysis was elaborated on the basis of experimentally determined kinetic parameters [81]. It was shown that the mutation-derived activity 

The classic interpretation of the development of neurodegeneration in the case of TPI deficiency is based upon the extensive inhibition of TPI activity by mutation, which prevents the adjustment of the physiological ratio of triosephosphates. Indeed, in erythrocytes, it results in the accumulation of DHAP. However, this may 

In brain tissues, specific isoforms of glycolytic enzymes are also expressed there are specific brain isoforms for PFK (PFK-C), fructose-1,6-bisphosphate aldolase (aldolase C), enolase (enolase y), but not for GAPDH. The isoforms bear the same catalytic functions however, they could be specialized to form different ultrastructural entities. For example, muscle PFK (a dissociable tetrameric form) binds to microtubules and bundle them [94, 95], however, the brain isoenzyme (stable tetramer) does not [96]. 

---

Triosephosphate Isomerase Deficiency, a Unique Glycolytic Enzymopathy I 245... 

---